Bone Changes in Pre- and Postmenopausal Women with Thyroid Cancer on Levothyroxine Therapy: Evolution of Axial and Appendicular Bone Mass

Abstract

The effects of suppressive doses of levothyroxine (LT4) on bone mass are controversial. Our aim was to evaluate the effects on axial and appendicular bone mineral density (BMD) and bone metabolism of long-term LT4 suppressive therapy in women by means of cross-sectional and longitudinal studies, and also to assess the potential influence of menopausal status and LT4 dose. Seventy-six women (aged 47 +/- 13 years, 37 pre- and 39 postmenopausal) on suppressive therapy (67 +/- 34 months duration, mean LT4 dose 168 +/- 41 micrograms/day) from our Thyroid Cancer Unit without previous hyperthyroidism or concomitant hypoparathyroidism were studied. Serum TSH, T3 free T4, calcium, phosphorus, alkaline phosphatase, BGP, iPTH and urinary calcium (uCA) were measured. BMD was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine, femoral neck, Ward's triangle, ultradistal and distal third radius and expressed as a Z-score. In a subset of 27 women aged 46 +/- 15 years (14 pre- and 13 postmenopausal) a second densitometry scan was performed 27 +/- 5 months later. Patients on suppressive therapy showed a small reduction in BMD at the distal third radius (Z-score: -0.77 +/- 0.98; 95% confidence interval: -1.11, -0.44) without differences between pre- and postmenopausal women. Significant relations with the regimen of suppressive therapy and bone turnover markers were detected except at the lumbar spine. In the longitudinal study a significant although mild reduction in femoral neck BMD was found that correlated with prior T3 and iPTH. In conclusion, our data show a small detrimental effect of cautious LT4 suppressive therapy on bone mass assessed by DXA; it remains to be established whether this increases the prevalence of fractures.

Bone mineral density and bone microarchitecture after long-term suppressive levothyroxine treatment of differentiated thyroid carcinoma in young adult patients

“…Previous studies in patients with well-differentiated thyroid cancer receiving suppressive LT 4 therapy have shown conflicting results: no decrease in BMD at any age [5,6], bone loss only in postmenopausal women [17], or deleterious effects in both premenopausa and postmenopausal patients [18,19]. Systematic reviews of BMD in these patients have reported diverse conclusions [3,4].…”

The skeletal consequences of thyrotoxicosis

“…Nevertheless, two reported metaanalyses have suggested that suppressive doses of T 4 in postmenopausal women lead to increased bone loss of w1% per annum (Faber & Galloe 1994, Uzzan et al 1996. Eight studies have also included male patients, but only one reported a reduction of BMD in men receiving suppressive doses of T 4 (Jodar et al 1998). Consistent with this, a metaanalysis concluded that suppressive doses of T 4 had no effect on BMD in men (Uzzan et al 1996).…”

Serum osteoprotegerin and soluble receptor activator of nuclear factor κB ligand levels in patients with a history of differentiated thyroid carcinoma: a case-controlled cohort study

“…The increase in OPG with age and markers of bone turnover further confirms the protective role of the cytokine against bone loss [42]. The cause of bone loss after long-term sustained hyperthyroxinemia [21,25,[28][29][30]53] will be more extensively studied in the light of new knowledge on the OPG and RANK/RANK-L systems. Finally, the controversial extrathyroid action of TSH on bone [54] must be considered in this new scenario.…”

“…The effect of subclinical hyperthyroidism on bone mineral density (BMD) is controversial [25][26][27], but could be significant in patients with differentiated thyroid carcinoma (DTC) who receive suppressive long-term doses of levothyroxine (L-T4) after total thyroidectomy [28,29]. Some authors [30] have shown that L-T4 suppressive therapy for at least 1 year in premenopausal women with DTC causes a reduction in BMD of the femoral neck, femoral trochanter, and Ward's triangle, whereas others [31,32] were unable to exclude the possibility that long-term suppressive doses of L-T4 do not decrease BMD.…”